Journal of Orthopaedic Translation最新文献

{"title":"Identification and function of periosteal skeletal stem cells in skeletal development, homeostasis, and disease","authors":"Fan Shi ,&nbsp;Guixin Yuan ,&nbsp;Zuoxing Wu ,&nbsp;Zhengqiong Luo ,&nbsp;Zihan Chen ,&nbsp;Qian Liu ,&nbsp;Na Li ,&nbsp;Ren Xu","doi":"10.1016/j.jot.2025.01.010","DOIUrl":"10.1016/j.jot.2025.01.010","url":null,"abstract":"<div><h3>Background</h3><div>Periosteum-resident skeletal stem cells (SSCs) are essential for the growth, maintenance, and repair of the skeletal system. These cells exhibit self-renewal ability and clonal pluripotency. Compared to the diverse bone marrow mesenchymal stem cells (BMSCs), periosteal skeletal stem cells (P-SSCs) represent a purified stem cell population and are preferable for bone tissue engineering.</div></div><div><h3>Methods</h3><div>This review covers the histological structure of the periosteum, process of isolating and characterising P-SSCs, and spatiotemporal distribution and characteristics of P-SSCs from different lineages. Additionally, the roles of P-SSCs in bone injury, disease, and periosteal niche regulation are discussed.</div></div><div><h3>Results</h3><div>Intramembrane and intraconal ossification of P-SSCs exhibits favourable therapeutic potential. Osteogenesis using P-SSCs is an ideal process for bone repair.</div></div><div><h3>Conclusions</h3><div>P-SSCs are vital for bone formation, maintenance, and repair. P-SSCs are essential components of the periosteal microenvironment. Therefore, it is essential to investigate their critical clinical applications and translational functions. By targeting and inducing endogenous stem cells, the in situ repair of bone defects can be facilitated, leading to the development of more effective novel therapies.</div></div><div><h3>The translational potential of this article</h3><div>To enhance our understanding of the function of P-SSCs in bone repair and skeleton-related diseases, it is imperative to elucidate the current research status of P-SSCs and ascertain the prospective trajectory for their advancement and refinement in bone tissue engineering. P-SSCs are expected to play an expanded role in treating bone abnormalities, leading to the optimisation of bone tissue treatment.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 177-186"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T cell related osteoimmunology in fracture healing: Potential targets for augmenting bone regeneration","authors":"Haixing Wang ,&nbsp;Yashi Li ,&nbsp;Haoxin Li ,&nbsp;Xu Yan ,&nbsp;Zhaowei Jiang ,&nbsp;Lu Feng ,&nbsp;Wenhui Hu ,&nbsp;Yinuo Fan ,&nbsp;Sien Lin ,&nbsp;Gang Li","doi":"10.1016/j.jot.2024.12.004","DOIUrl":"10.1016/j.jot.2024.12.004","url":null,"abstract":"<div><div>Last decade has witnessed increasing evidence which highlights the roles of immune cells in bone regeneration. Numerous immune cell types, including macrophages, T cells, and neutrophils are involved in fracture healing by orchestrating a series of events that modulate bone formation and remodeling. In this review, the role of T cell immunity in fracture healing has been summarized, and the modulatory effects of T cell immunity in inflammation, bone formation and remodeling have been highlighted. The review also summarizes the specific roles of different T cell subsets, including CD4⁺ T cells, CD8⁺ T cells, regulatory T cells, T helper 17 cells, and γδ T cells in modulating fracture healing. The current therapeutics targeting T cell immunity to enhance fracture healing have also been reviewed, aiming to provide insights from a translational standpoint. Overall, this work discusses recent advances and challenges in the interdisciplinary research field of T cell related osteoimmunology and its implications in fracture healing.</div></div><div><h3>The translational potential of this article</h3><div>Delayed unions or non-unions of bone fractures remain a challenge in clinical practice. Developing a deep understanding of the roles of immune cells, including T cells, in fracture healing will facilitate the advancement of novel therapeutics of fracture nonunion. This review summarizes the current understanding of different T cell subsets involved in various phases of fracture healing, providing insights for targeting T cells as an alternative strategy to enhance bone regeneration.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 82-93"},"PeriodicalIF":5.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Piezoelectric biomaterials for providing electrical stimulation in bone tissue engineering: Barium titanate","authors":"Huagui Huang ,&nbsp;Kaizhong Wang ,&nbsp;Xiangyan Liu ,&nbsp;Xin Liu ,&nbsp;Jinzuo Wang ,&nbsp;Moran Suo ,&nbsp;Hui Wang ,&nbsp;Shuang Chen ,&nbsp;Xin Chen ,&nbsp;Zhonghai Li","doi":"10.1016/j.jot.2024.12.011","DOIUrl":"10.1016/j.jot.2024.12.011","url":null,"abstract":"<div><div>With the increasing clinical demand for orthopedic implants, bone tissue engineering based on a variety of bioactive materials has shown promising applications in bone repair. And various physiological cues, such as mechanical, electrical, and magnetic stimulation, can influence cell fate and participate in bone regeneration. Natural bone has a piezoelectric effect due to the non-centrosymmetric nature of collagen, which can aid in cell adhesion, proliferation and differentiation, and bone growth by converting mechanical stimuli into electrical stimuli. Piezoelectric materials have the same piezoelectric effect as human bone, and they are able to deform in response to physiological movement, thus providing electrical stimulation to cells or damaged tissue without the need for an external power source. Among them, Barium titanate (BaTiO₃) is widely used in tumor therapy, tissue engineering, health detection and drug delivery because of its good biocompatibility, low cytotoxicity and good piezoelectric properties. This review describes the piezoelectric effect of natural bone and the characteristics of various types of piezoelectric materials, from the synthesis and physicochemical characteristics of BaTiO₃ and its application in biomedicine. And it highlights the great potential of BaTiO₃ as piezoelectric biomaterials in the field of bone tissue engineering in anticipation of providing new ideas and opportunities for researchers.</div><div><strong>The translational potential of this article</strong>: This review systematically discusses barium titanate, a bioactive material that can mimic the piezoelectric effect of natural bone tissue, which can intervene in the regenerative repair of bone by providing a sustained electrical microenvironment for bone repair scaffolds. This may help to solve the current problem of poor osteogenic properties of bioactive materials by utilizing barium titanate.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 94-107"},"PeriodicalIF":5.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast growth factor receptor 3 mutation promotes HSPB6-mediated cuproptosis in hypochondroplasia by impairing chondrocyte autophagy","authors":"Jing Chen ,&nbsp;Dan He ,&nbsp;Chengrun Yuan ,&nbsp;Na Li ,&nbsp;Baohong Shi ,&nbsp;Conway Niu ,&nbsp;Jiangfei Yang ,&nbsp;Liangkai Zheng ,&nbsp;Lin Che ,&nbsp;Ren Xu","doi":"10.1016/j.jot.2025.01.011","DOIUrl":"10.1016/j.jot.2025.01.011","url":null,"abstract":"<div><h3>Background</h3><div>Hypochondroplasia (HCH) is a prevalent form of dwarfism linked to mutations in the fibroblast growth factor receptor 3 (<em>FGFR3</em>) gene, causing missense alterations. We previous report was the first to identify <em>FGFR3</em>(G382D) gain-of-function variants with a positive family history as a novel cause of HCH. However, the precise contribution of <em>FGFR3</em> to the pathogenesis of HCH remains elusive.</div></div><div><h3>Methods</h3><div>We generated an <em>Fgfr3</em> (V376D) mutation mouse model using CRISPR/Cas9 technology and performed proteomic analyses to investigate the molecular mechanisms and potential therapeutic targets of HCH. Radiography and micro-computed tomography were employed to assess the bone-specific phenotype in <em>Fgfr3</em> <em>(V376D)</em>mutant mice. Immunofluorescence, western blotting, and flow cytometry were used to systematically investigate the underlying mechanisms and therapeutic targets.</div></div><div><h3>Results</h3><div>We observed that <em>Fgfr3</em> (V376D) mutant mice exhibit a bone-specific phenotype, with symmetrically short limb bones, partially resembling the dwarfism phenotype of patients with HCH. We demonstrated that the mutant-activated FGFR3 promotes heat shock protein B 6 (HSPB6)-mediated cuproptosis by inhibiting chondrocyte autophagy both <em>in vivo</em> and <em>in vitro</em>. Additionally, we revealed that <em>FGFR3</em> (G382D) mutation leads to enhanced ERK signaling, increased Drp1-mediated mitochondrial fission, and upregulated cuproptosis-related protein ferredoxin 1 (FDX1). Furthermore, genetic and pharmacological inhibition of the HSPB6-ERK-Drp1-FDX1 pathway partially alleviate the phenotypes of <em>FGFR3</em> mutants.</div></div><div><h3>Conclusions</h3><div>Our study provides the first evidence for the pathogenicity of a gain-of-function mutation in <em>FGFR3</em> (G382D) using mouse and cell models, and it underscores the potential of targeting the HSPB6-ERK-Drp1-FDX1 axis as a novel therapeutic approach for HCH.</div></div><div><h3>Translational potential of this article</h3><div>We first demonstrate that impaired autophagy and enhanced cuproptosis are pivotal in the pathogenesis of HCH. This study not only enlarged the therapeutic potential of targeting cuproptosis for treating <em>FGFR3</em> mutation-related HCH but also provided a novel perspective on the role of the HSPB6-ERK-Drp1-FDX1 signaling pathway in the development of HCH. Consequently, this article provides valuable insights into the mechanisms and treatment strategies for <em>FGFR3</em> mutation-related chondrodysplasia.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 68-81"},"PeriodicalIF":5.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autologous osteoperiosteal transplantation achieves comparable repair effect and superior interface integration to autologous osteochondral transplantation in porcine osteochondral defects","authors":"Shuai Yang ,&nbsp;En Deng ,&nbsp;Linxin Chen ,&nbsp;Yanbin Pi ,&nbsp;Anhong Wang ,&nbsp;Linghui Dai ,&nbsp;Hongjie Huang ,&nbsp;Xiaoning Duan ,&nbsp;Xin Fu ,&nbsp;Jiying Zhang ,&nbsp;Qinwei Guo ,&nbsp;Weili Shi","doi":"10.1016/j.jot.2024.12.005","DOIUrl":"10.1016/j.jot.2024.12.005","url":null,"abstract":"<div><h3>Background</h3><div>Autologous osteochondral transplantation (AOCT) has been established as an effective treatment strategy for osteochondral defects. Additionally, autologous osteoperiosteal transplantation (AOPT) has emerged as a promising alternative with comparable clinical efficacy. However, a notable gap in the literature exists regarding the specific repair process by the periosteal graft. Therefore, the primary objective of the present study was to assess the osteochondral repair efficacy of AOPT using a porcine model and to elucidate the repair process of the periosteal graft.</div></div><div><h3>Hypothesis</h3><div>AOPT would achieve similar repair effect to AOCT and the grafted periosteum would progressively transform into cartilage-like tissue.</div></div><div><h3>Methods</h3><div>Cylindrical osteochondral defects (8.0 mm in diameter and 5.0 mm in depth) were surgically created bilaterally at the center of the medial femoral condyles in 27 Guangxi Bama minipigs. The 54 knees were randomly allocated into three groups: negative control (n = 18), AOCT (n = 18), and AOPT (n = 18). Osteochondral grafts were harvested from non-weightbearing area of the femoral notch, while osteoperiosteal grafts were from the ipsilateral iliac crest. At 2, 4, and 6 months post-surgery, the knees were subjected to macroscopic, radiographic, nanoindentation and histological evaluations.</div></div><div><h3>Results</h3><div>At 2, 4, and 6 months postoperatively, the gross view evaluation using the International Cartilage Repair Society (ICRS) scoring system and the imaging assessment with the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system showed similar results in the AOCT and AOPT groups, both superior to those of the control group. Nanoindentation analysis revealed near-normal biomechanical properties in the repaired cartilage of both AOPT and AOCT groups. Histological evaluation indicated that the quality of repaired tissues in the AOPT group was comparable to that in the AOCT group. Notably, AOPT consistently exhibited superior interface integration compared to AOCT at all time points.</div></div><div><h3>Conclusion</h3><div>Both AOPT and AOCT demonstrate significant efficacy in promoting the repair of osteochondral defects in a porcine model. Despite similar radiographic findings, mechanical performance and histological structure displayed in both grafted groups, AOPT exhibit superior interface integration, which is critical for effective tissue restoration.</div></div><div><h3>The translational potential of this article</h3><div>As a recently developed procedure for treating osteochondral defects, AOPT has shown promising repair effect and is being increasingly adopted in clinical practice. This study presents histological evidence of the progressive transformation of the periosteum graft into cartilage-like tissue and demonstrates its ability to integrate with the surrounding tissue.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 59-67"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vibration therapy as an intervention for trochanteric hip fractures – A randomized double-blinded, placebo-controlled trial","authors":"Ronald Man Yeung Wong ,&nbsp;Pui Yan Wong ,&nbsp;Chaoran Liu ,&nbsp;Chun Sing Chui ,&nbsp;Wing Hong Liu ,&nbsp;Ning Tang ,&nbsp;James Griffith ,&nbsp;Ning Zhang ,&nbsp;Wing Hoi Cheung","doi":"10.1016/j.jot.2025.01.002","DOIUrl":"10.1016/j.jot.2025.01.002","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Hip fractures are one of the most serious forms of fragility fractures. Low-magnitude high-frequency vibration (LMHFV) is a biophysical intervention that provides non-invasive, systemic mechanical stimulation. The objectives of this study were to investigate the efficacy of LMHFV in trochanteric hip fracture elderly patients to (i) accelerate trochanteric fracture healing and (ii) improve clinical and functional outcomes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A randomized double-blinded, placebo-controlled clinical trial was conducted. Participants were randomly assigned into LMHFV or placebo intervention for 14 days. Primary outcome assessments were fracture healing assessed with CT scan and X-rays. Dual X-ray Absorptiometry (DXA) scan was performed to assess bone mineral density change. Secondary outcome assessments were clinical and functional outcomes with quadriceps muscle strength, balancing ability, handgrip strength, Time Up and Go (TUG) test, quality of life outcomes, pain, falls, and mortality.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;237 patients were screened for eligibility by the inclusion and exclusion criteria. 62 patients were recruited and randomly assigned to placebo group (n = 32, mean age: 83.6 ± 7.0 years, women: 71.9 %) or LMHFV group (n = 30, mean age: 81.5 ± 5.7 years, women: 73.3 %). For fracture healing, CT scan at 6 weeks showed improved osseous union for the LMHFV group at 71.5 ± 19.4 % compared to placebo group at 58.8 ± 30.5 %, but no statistical significance detected. X-rays showed fractures healed at 12 months. LMHFV group had significantly higher quadriceps muscle strength compared to placebo group on affected leg using maximum reading (week 26: 8.8 ± 3.6 kg vs. 6.1 ± 4.1 kg; p = 0.011) and average reading (week 26: 8.0 ± 3.7 kg vs. 5.2 ± 3.3 kg; p = 0.008) amongst 3 trials. The balancing ability test could not be performed in most of the subjects at the baseline measurement. However, from week 6 to week 26, LMHFV group had significantly improved balancing compared to placebo group for overall stability index (week 26: 1.6 ± 1.1 vs. 3.4 ± 2.6; p = 0.006), anteroposterior stability index (week 26: 1.1 ± 0.7 vs. 2.1 ± 1.9; p = 0.048) and medial-lateral stability index (week 26: 0.9 ± 0.7 vs. 2.2 ± 2.2; p = 0.008). There was a significant increase in success in performing TUG test in LMHFV group from baseline (13.3 %) to 26 weeks (57.1 %) (p = 0.004). Quality-of-life outcomes by SF-36 showed LMHFV group had a significant improvement at a score of 62.1 ± 18.9 compared to control group at a score of 48.5 ± 18.9 after adjusting for the baseline measurement (p = 0.044).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;A short duration of LMHFV during in-patient stay can improve clinical outcomes and can potentially be incorporated as a practical measure during the recovery of fragility hip fractures.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;div&gt;14 days of LMHFV treatment is gen","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 51-58"},"PeriodicalIF":5.9,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-speed centrifugation reduces immune rejection by removing bone marrow elements from fresh osteochondral allografts","authors":"Yongsheng Ma ,&nbsp;Wenming Yang ,&nbsp;Qitai Lin ,&nbsp;Meiming Li ,&nbsp;Zehao Li ,&nbsp;Yugang Xing ,&nbsp;Lei Wei ,&nbsp;Wangping Duan ,&nbsp;Xiaochun Wei","doi":"10.1016/j.jot.2024.12.008","DOIUrl":"10.1016/j.jot.2024.12.008","url":null,"abstract":"<div><h3>Background</h3><div>Fresh osteochondral allografts (OCAs) contain numerous immunogenic components in the subchondral bone (SB). Whether high-speed centrifugation (HSC) reduces immune rejection by removing bone marrow elements (BMEs), compared to methods without HSC, remains unknown. This study aimed to validate the efficacy and safety of HSC in reducing immune rejection by removing allogeneic BMEs.</div></div><div><h3>Methods</h3><div>OCAs were obtained from the femoral condyles of the stifle joint in 18 pigs. Gross observations, histological staining, weight measurements, and DNA extraction were performed to assess the effects of centrifugation speed and duration on BMEs removal in OCAs. The effect of HSC on OCAs preservation was determined in vitro using microbiological testing, live/dead cell staining, and histological staining. Moreover, the co-culture effect of RAW264.7 cells and OCAs with or without HSC in vitro was evaluated using enzyme-linked immunosorbent assay (ELISA), histological staining, and immunohistochemical staining. The transplantation effect of OCAs with or without HSC was examined in vivo using a subcutaneous mouse model. Finally, the residues in the centrifuge tubes were analysed using ELISA, haematoxylin and eosin (HE) staining, and metabolomic analysis.</div></div><div><h3>Results</h3><div>Centrifugal speeds of 12000 rpm for 1 min were sufficient to reduce BMEs by over 90 %. HSC had a protective effect on chondrocytes and the extracellular matrix during the in vitro preservation of OCAs. In addition, OCAs using the HSC method exhibited reduced recognition by the host immune system compared with OCAs without HSC, thereby reducing immune rejection. Lipids were the most abundant and difficult-to-remove antigenic components and are the most likely to affect host macrophage polarisation, playing an important role in immune rejection.</div></div><div><h3>Conclusion</h3><div>Our study demonstrated that HSC method significantly reduces immune rejection by removing BMEs from OCAs.</div></div><div><h3>The translational potential of this article</h3><div>Our study demonstrated that HSC is a simple, efficient, and safe physical method for removing antigenic components from OCAs, effectively reducing immune rejection and highlighting its clinical potential.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 37-50"},"PeriodicalIF":5.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accumulation of advanced oxidation protein products aggravates bone-fat imbalance during skeletal aging","authors":"Yu-Sheng Huang ,&nbsp;Jia-Wen Gao ,&nbsp;Rui-Feng Ao ,&nbsp;Xin-Yu Liu ,&nbsp;Di-Zheng Wu ,&nbsp;Jun-Long Huang ,&nbsp;Chen Tu ,&nbsp;Jing-Shen Zhuang ,&nbsp;Si-Yuan Zhu ,&nbsp;Zhao-Ming Zhong","doi":"10.1016/j.jot.2024.12.010","DOIUrl":"10.1016/j.jot.2024.12.010","url":null,"abstract":"<div><h3>Background</h3><div>Skeletal aging is characterized by a decrease in bone mass and an increase in marrowfat content. Advanced oxidation protein products (AOPPs) accumulate easily with aging and disrupt redox homeostasis. We examined whether AOPPs accumulation contributes to the bone-fat imbalance during skeletal aging.</div></div><div><h3>Methods</h3><div>Both young and aged mice were employed to assess the changes of AOPPs levels and its contribution to bone-fat imbalance during skeletal aging. Primary bone marrow mesenchymal stromal cells (MSCs) were used to examine the potential role of AOPPs in age-related switch between osteogenic and adipogenic differentiation. Aged mice were also gavaged by non-selective antioxidant N‐acetyl‐L‐cysteine (NAC), followed by close monitoring of the changes in AOPPs levels and bone-fat metabolism. Furthermore, young mice were chronically exposed to AOPPs and then evaluated for the changes of bone mass and marrow adiposity.</div></div><div><h3>Results</h3><div>The levels of AOPPs in serum and bone marrow were markedly higher in aged mice than that in young mice. Age-related accumulation of AOPPs was accompanied by reduced bone formation, increased marrow adiposity and deterioration of bone microstructure. Reduced AOPPs accumulation by antioxidant NAC leaded to improvement of the bone-fat imbalance in aged mice. Similarly, the bone-fat imbalance was induced by chronic AOPPs loading in young mice. Compared with MSCs from young mice, MSCs from aged mice tended to differentiate into adipocytes rather than osteoblasts and displayed cellular senescence. Exposure of primary MSCs to AOPPs resulted in the switch from osteogenic to adipogenic lineage and cellular senescence. AOPPs challenge also increased intracellular ROS generation by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and mitochondria. The antioxidant NAC, after scavenging ROS, ameliorated the AOPPs-induced lineage switch and senescence in MSCs by inhibiting the PI3K/AKT/mTOR pathway.</div></div><div><h3>Conclusion</h3><div>Our findings revealed the involvement of AOPPs in age‐related switch between osteogenic and adipogenic differentiation, and illuminated a novel potential mechanism underlying bone-fat imbalance during skeletal aging.</div></div><div><h3>The translational potential of this article</h3><div>Reducing AOPPs accumulation and its cascading effects on MSCs might be an attractive strategy for delaying skeletal aging.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 24-36"},"PeriodicalIF":5.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of YAP/TAZ in bone diseases: A transductor from mechanics to biology","authors":"Xin Chen ,&nbsp;Xing Ji ,&nbsp;Zhaobai Lao ,&nbsp;Bin Pan ,&nbsp;Yu Qian ,&nbsp;Wanlei Yang","doi":"10.1016/j.jot.2024.12.003","DOIUrl":"10.1016/j.jot.2024.12.003","url":null,"abstract":"<div><div>Wolff's Law and the Mechanostat Theory elucidate how bone tissues detect and convert mechanical stimuli into biological signals, crucial for maintaining bone equilibrium. Abnormal mechanics can lead to diseases such as osteoporosis, osteoarthritis, and nonunion fractures. However, the detailed molecular mechanisms by which mechanical cues are transformed into biological responses in bone remain underexplored. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), key regulators of bone homeostasis, are instrumental in this process. Emerging research highlights bone cells' ability to sense various mechanical stimuli and relay these signals intracellularly. YAP/TAZ are central in receiving these mechanical cues and converting them into signals that influence bone cell behavior. Abnormal YAP/TAZ activity is linked to several bone pathologies, positioning these proteins as promising targets for new treatments. Thus, this review aims to provide an in-depth examination of YAP/TAZ's critical role in the interpretation of mechanical stimuli to biological signals, with a special emphasis on their involvement in bone cell mechanosensing, mechanotransduction, and mechanoresponse.</div><div>The translational potential of this article: Clinically, appropriate stress stimulation promotes fracture healing, while bed rest can lead to disuse osteoporosis and excessive stress can cause osteoarthritis or bone spurs. Recent advancements in the understanding of YAP/TAZ-mediated mechanobiological signal transduction in bone diseases have been significant, yet many aspects remain unknown. This systematic review summarizes current research progress, identifies unaddressed areas, and highlights potential future research directions. Advancements in this field facilitate a deeper understanding of the molecular mechanisms underlying bone mechanics regulation and underscore the potential of YAP/TAZ as therapeutic targets for bone diseases such as fractures, osteoporosis, and osteoarthritis.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 13-23"},"PeriodicalIF":5.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperbaric oxygen potentiates platelet-rich plasma composition and accelerates bone healing","authors":"Wen-Shuo Chang ,&nbsp;Chien-Cheng Huang ,&nbsp;Tzu-Hao Chen ,&nbsp;Ssu-Han Chao ,&nbsp;Cheng-Hsien Lin ,&nbsp;Ching-Ping Chang ,&nbsp;Chi-Sheng Chien","doi":"10.1016/j.jot.2024.10.016","DOIUrl":"10.1016/j.jot.2024.10.016","url":null,"abstract":"<div><h3><em>Objective</em></h3><div>This study aimed to investigate whether platelet-rich plasma (PRP) obtained from the blood of rats preconditioned with hyperbaric oxygen (HBOP) would enhance the biological activity of PRP and accelerate the healing process of femur fractures in a rat model.</div></div><div><h3><em>Design</em></h3><div>PRP was derived from blood samples of healthy rats subjected to either hyperbaric oxygen (hPRP) or normobaric air (nPRP). A closed femur fracture model was established in male Wistar rats, with treatments of hPRP or nPRP administered around the fracture site immediately post-fracture and on days 7, 14, 21, and 28. Growth factor concentrations in hPRP and nPRP were biochemically quantified. Bone healing was assessed weekly by X-ray, while histological and immunofluorescence analyses evaluated inflammatory status, osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL) expression, and the presence of osteoblasts, osteoclasts, and osteocytes during healing. The effects of hPRP and nPRP on MC3T3-E1 preosteoblast migration and proliferation were also tested <em>in vitro</em>.</div></div><div><h3><em>Results</em></h3><div>hPRP showed significantly higher concentrations of growth factors such as activin-A, brain-derived neurotrophic factor, nerve growth factor, Flt-3 Ligand, granulocyte-macrophage colony-stimulating factor, hepatocyte growth factor, and platelet-derived growth factor, compared to nPRP. <em>In vitro</em>, hPRP demonstrated more significant effects on preosteoblast migration and proliferation. <em>In vivo</em>, hPRP treatment resulted in enhanced bone healing, higher OPG levels in osteoblasts and osteoclasts, and an elevated OPG/RANKL ratio compared to nPRP.</div></div><div><h3><em>Conclusions</em></h3><div>HBOP enhances the biological activity of PRP and accelerates bone healing in a closed femur fracture model in rats. This study highlights the regenerative potential of PRP when preconditioned with hyperbaric oxygen for use in bone fracture therapy.</div></div><div><h3><em>Significance statement</em></h3><div>PRP is widely used in treating bone defects and fractures, but its enhancement through HBOP remains underexplored. Our findings demonstrate that HBOP potentiates the biological activity of PRP, offering promising therapeutic potential for bone fracture healing.</div></div><div><h3><em>The translational potential of this article</em></h3><div>Enriching growth factors in PRP through HBOP could significantly improve tissue regeneration, especially in bone healing. The potential of hPRP in clinical applications is highly promising, particularly in orthopaedic surgery, trauma care, sports medicine, and managing bone healing in compromised patients.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 1-12"},"PeriodicalIF":5.9,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}